Timothy O'Shea, PharmD
Timothy O'Shea, PharmD
Timothy O'Shea, PharmD, is a Clinical Pharmacist working at a large health insurance plan on the east coast. Additionally he works per diem at a retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.

5 Interesting Medication Case Reports - Part 3

APRIL 26, 2017
This article is part 3 of a 6-part series on interesting and unusual medication-related case reports. For part 2 click here
 
Case reports are defined as the scientific documentation of an individual patient. These reports are often written to document an unusual clinical presentation, treatment approach, side effect, or response to treatment. Most experts see case reports as the first line of evidence in health care, which can sometimes lead to future higher-level studies.
 
Case reports can be a great learning opportunity for both pharmacists and pharmacy students to understand a case progression and the unconventional response and effects of medications.
 
This article highlights 5 published case reports that document unusually high doses of medications that are not often seen in clinical practice.
 
1. High dose methylphenidate treatment for ADHD1
Attention-deficit hyperactivity disorder (ADHD) is a prevalent mental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. While treatment of ADHD focuses around both psychotherapeutic and pharmacologic interventions, stimulant medications are considered first-line treatment in both pediatrics and adults. Methylphenidate (MPH) is one stimulant that is available in a number of formulations including tablet, capsule, solution, patch, and powder for suspension.
 
In 2012, a case report was published about a 38-year-old Caucasian male who was diagnosed with ADHD when he was 9 years old. He had a comorbid history of obsessive compulsive disorder (OCD) and a combined personality disorder. Initially, the patient received 10 mg of immediate-release MPH as a child that was then increased to 20 mg of sustained-release MPH. Later, the MPH was discontinued and replaced with desipramine. During a near 20-year stretch marked with symptoms of ADHD leading to several failed attempts to finish college, the patient was started on 60 mg per day of immediate-release MPH.
 
This new regimen was reported as highly effective, but it did not maintain control through the course of a day. During the following 14 months, the patient began excessively using MPH both orally and rectally in doses up to 4800-6000 mg per day. The patient was eventually referred to an outpatient service for management of stimulant dependence. The patient reported no signs of palpitations, tachycardia, or dyspnea and clinicians found no abnormalities with his heart rate or ECG. Under close doctor supervision, the patient received 200 mg per day of immediate-release MPH, which was later increased to 378 mg of extended-release MPH with notation of positive symptom control. Plasma levels of MPH were found to be within normal range. No further excessive use of MPH was reported for the next 24 months.
 
Researchers hypothesized that the patient may have had a gene variant that led to an increased enzyme activity that metabolizes MPH, although no genetic testing is available to confirm or deny this assumption.
 
2. Ultra-high dose sildenafil abuse2
Sildenafil (Viagra) is a phosphodiesterase-5 inhibitor that is FDA approved for the treatment of erectile dysfunction (ED). It is available as a tablet in strengths of 25 mg, 50 mg, and 100 mg. The maximum recommended dose is 100 mg per day.
 
A 2015 case report was published documenting the case of a 40-year-old man who administered sildenafil for 10 years at extremely high doses. The patient was an illiterate farmer who reported being unable to sustain an erection for more than 1 minute starting at age 28.  He married at age 30 and both he and his partner reported a lack of sexual satisfaction despite normal levels of interest and drive. The patient then consulted a psychiatrist who prescribed 100 mg of sildenafil prior to intercourse.
 
With sildenafil use, the patient was able to achieve an erection from 1 to 5 minutes; however, the benefit waned within several months. As a result, he started increasing the dose of the medication on his own and by age 38, he was taking 8-9 tablets of sildenafil 100 mg per occasion. At the time of consultation, he was self-medicating at a dose of 1300 mg per occasion, several times per week, which allowed him to sustain an erection for up to 5 minutes.
 
Upon consultation, the patient reported experiencing transient blurred vision within 20 minutes of sildenafil ingestion. He stated this effect had been present for the past 2 years, only on days of sildenafil use. The patient received a physical examination, comprehensive laboratory workup, and ophthalmological examination; all identified no abnormalities. No underlying cause could be identified for the patient’s ED. The authors state that this case represents that highest dose of chronic sildenafil that has ever been recorded in the literature.
 
3. High dose OxyContin for a cancer patient3
OxyContin (oxycodone extended-release) is a long-acting opioid analgesic FDA approved for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment. Pain in patients with cancer is a commonly reported symptom; in fact, nearly all patients with malignant tumors are expected to suffer pain at the advanced stage of their disease. Oxycodone, in both its immediate and extended-release formulation, is often used for treating moderate-to-severe cancer pain.
 
A recent article was published reporting the use of high-dose OxyContin to treat pain in a patient with small-cell lung cancer (SCLC) and bone metastasis. The patient was a 57-year-old man who was hospitalized for chemotherapy nearly 2 years after being diagnosed with SCLC in the left lung. Over the next few years, the patient cycled through a number of chemotherapy regimens, many of which were terminated due to poor compliance.
 
Initially, the patient was given ibuprofen for shoulder pain with minimal effect. Due to pain in the neck, shoulder, chest, and back the patient was given a prescription for OxyContin with titration starting at 10 mg every 12 hours. Three months later, the dose was gradually increased to 660 mg every 12 hours; however, the patient experienced acid reflux with no improvement in pain management. The doctor then switched the patient to OxyContin 600 mg every 8 hours with 50 mg of morphine immediate-release, 2-5 tablets per day, for breakthrough pain.
 
This regimen greatly improved the patient’s pain control, although he did report urinary retention as an adverse reaction. No signs of respiratory depression or mental symptoms were noted. The patient died later that year due to the lung cancer. The authors state that this case represents the importance of personalized treatment of cancer pain to improve quality of life, relieve pain, and help prolong patient survival.
 
 4. Ultra-high dose of long-acting injectable aripiprazole4
Over recent years, long-acting injectable (LAI) antipsychotics have been used with increased frequency for the maintenance treatment of schizophrenia. Since 2002, intramuscular LAI aripiprazole has been commercially available for treating patients with schizophrenia that have established tolerance with the oral formulation. The recommended maintenance dose is 400 mg administered monthly as a single injection.
 
In 2015, researchers published a case report that documented a 72-year-old female who was treated by clinicians with LAI aripiprazole at a dose much higher than is recommended. The patient was frequently admitted to the hospital after suffering from episodes of chronic refractory schizophrenia, particularly excessive delusions, and concerns of self-harm. Previous medications tried included several courses of oral and intramuscular first and second generation antipsychotics, benzodiazepines, and mood stabilizers.
 
Due to concerns of medication non-adherence, the patient was started on LAI olanzapine with positive therapeutic effect; however, the medication was discontinued following a three-day coma from accidental intravascular administration. After recovery from this episode, she was started on oral aripiprazole and then converted to 300 mg of the LAI formulation. The patient subsequently experienced an acute and severely psychotic episode so clinicians increased her dose to 400 mg administered every 14 days under continuous plasma level monitoring.
 
With normal plasma levels and a lack of side effects, the dose was gradually escalated to 600 mg every 14 days and later 800 mg every 3 weeks, with a positive control of symptoms. The authors state that to their knowledge, this case report represents the highest documented dose of LAI aripiprazole for chronic refractory schizophrenia, and call for researchers to further explore this type of dosing regimen.
 
5. High dose zolpidem dependence5
Zolpidem (Ambien) is a gamma-aminobutyric acid (GABA) A agonist, indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. It is available in a number of formulations including oral tablet, sublingual tablet, and mucous membrane spray. The maximum recommended dose is 10 mg per day of the immediate-release formulation and 12.5 mg with the extended-release tablet.
 
In 2007, a case report was published detailing one of the highest doses of zolpidem ever reported. The patient was a 34-year-old female who was prescribed zolpidem for sleep disturbance following a break-up with her ex-boyfriend. She had no previous history of psychiatric issues, substance abuse, or other disease. The patient gradually started to abuse the zolpidem and developed tolerance within 6 months. One year later, she increased the dose to 1000 mg per day.
 
Due to experiencing withdrawal symptoms when not taking zolpidem, including anxiety, hand tremor, sweating, and palpitation, she started taking the medication during the day. Two years after first starting zolpidem, she experienced a zolpidem withdrawal seizure. Despite several admissions for zolpidem detoxification, the patient relapsed soon after discharge. She was later sent to the emergency room for a generalized tonic-clonic seizure following three months of ingesting 2000 mg per day of zolpidem. A diazepam tapering regimen was used to treat the withdrawal symptoms and propranolol for hand tremor. She was discharged on chronic diazepam and trazodone and has been regularly followed.
 
The authors caution that clinicians should be cautious with the abuse potential of zolpidem and manage the psychiatric comorbidity aggressively.
 
References:
  1. Liebrenz M, Hof D, Buadze A, et al. High dose methylphenidate treatment in adult attention deficit hyperactivity disorder: a case report. J Med Case Rep. 2012 May 14;6:125. doi: 10.1186/1752-1947-6-125.
  2. Sathyanarayana Rao TS, Kumar VA, Raman R, Andrade C. Prolonged, longstanding, ultra-high-dose abuse of sildenafil. Indian Journal of Psychiatry. 2015;57(3):311-312. doi:10.4103/0019-5545.166626.
  3. Zhou T, Zhang X, Dong Y. High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report. Drug Des Devel Ther. 2016; 10: 383–387. Published online 2016 Jan 19. doi: 10.2147/DDDT.S97529.
  4. Bartova L, Dold M, Rieder NP, Heiden AN, Kasper S. Ultra-High-Dose Long-Acting Injectable Aripiprazole in Chronic Refractory Schizophrenia: A Case Report. J Clin Toxicol. 2015 Oct;15. 5:270. doi:10.4172/2161-0495.1000270.
  5. Huang M, Lin H, Chen C. Dependence on zolpidem. Psychiatry and Clinical Neurosciences. 2007. 61, 207–208. doi:10.1111/j.1440-1819.2007.01644.x.


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